Endocytosis is a fundamental biological process that is involved in numerous cellular functions including receptor cycling, metabolism and the entry of assorted macromolecules into the cell. Even though the process is highly regulated, the factors that direct the different macromolecules from the outside of the cell to their target sites in the cell are not well understood. Polypeptide motifs may be crucial in steering different proteins to different cellular compartments and/or different vesicles that comprise the endocytic pathway. The aim of this project is to characterize the endocytic pathway in cardiac myocytes, to identify specific peptide motifs that target endocytosis into cardiac myocytes as well as to define the pathways by which each mediates endocytosis, and to determine the role of Caveolin-3 (cav-3) in cardiac myocyte endocytosis. The methods will involve i) colocalization studies using fluorescent probes, ii) peptide and antibody phage display and bactria-based peptide display biopanning, iii) the study of cav-3 knockout mice. The discoverry of polypeptides that guide macromolecules to specific cellular organelles or compartments can have profound implications for understanding microbial invasion and for refining gene therapy.